Clinical Trial 18342

Cancer Type:
Interventions:G-CSF; MESNA; NY-ESO-1c259T; cyclophosphamide; cytoxan (cyclophosphamide)

Study Type: Treatment
Phase of Study: Phase I/II

  • Benjamin Creelan


Study Title

A Pilot Open Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects with Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)


The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in participants with lung cancer.


Primary: To evaluate the safety and tolerability of autologous genetically modified T cells (NY-ESO-1c259T) in HLA-A*0201, HLA-A*0205 and/or HLA-A*0206 positive subjects with NY-ESO-1 positive advanced NSCLC. Secondary: To evaluate the efficacy of NY-ESO-1c259T. To measure persistence of genetically modified cells in the body. To evaluate the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion. To evaluate NY-ESO-1 expression in tumor tissue, before and after treatment, and correlate with clinical response to treatment.

Inclusion Criteria

  • Participant has voluntarily agreed to participate by giving written informed consent in accordance with ICH GCP Guidelines and applicable local regulations.
  • ≥18 years of age.
  • Histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease.
  • Participants with known EGFR mutations or ALK or ROS1 gene rearrangements must have failed (PD or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). There is no limit to lines of prior anti-cancer therapy.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Is HLA-A*0201, HLA-A*0205 and/or HLA-A*0206 positive.
  • Participant's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming NY-ESO-1 expression by immunohistochemistry. Positive expression is defined as ≥50% of cells that are 2+ and/or 3+ by immunohistochemistry.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and anticipated life expectancy > 3 months.
  • Must have left ventricular ejection fraction ≥50%.
  • Is fit for leukapheresis and has adequate venous access for the cell collection.
  • Females of childbearing potential (FPCP) must have a negative urine or serum pregnancy test. FPCP must agree to use maximally effective birth control or to abstain from heterosexual activity throughout the study, starting at the first dose of chemotherapy through 18 months after the infusion of cells and until persistence of gene modified cells are not found in the blood. Or Male participants must be surgically sterile or agree to use a double barrier contraception method upon enrolment starting at the first dose of chemotherapy through at least 4 months after treatment.
  • Adequate organ function.
  • Have failed at least one prior platinum-containing regimen and have disease progression.

  • Exclusion Criteria

  • Has received cytotoxic chemotherapy within 3 weeks prior to leukapheresis.
  • Has received immune therapy (including monoclonal antibody therapy, checkpoint inhibitors) or biological therapy within 4 weeks prior to leukapheresis.
  • Has received corticosteroids or any other immunosuppressive therapy within 2 weeks prior to leukapheresis; NOTE: recent or current use of inhaled or topical steroids is not exclusionary.
  • Tyrosine kinase inhibitor (e.g. erlotinib, gefitinib) and any other anti-cancer treatment within 1 week prior to leukapheresis.
  • Investigational treatment within 4 weeks prior to leukapheresis.
  • Experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis.
  • Any prior gene therapy using an integrating vector.
  • Toxicity from previous anti-cancer therapy that has not recovered to ≤Grade 1 (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Participants with existing pneumonitis as a result of radiation are not excluded; however, participants cannot be oxygen dependent.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludaragine, or other agents used in the study.
  • History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
  • Has active brain metastases or leptomeningeal metastases. Potential participants with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to screening are eligible.
  • Other active malignancies besides NSCLC within 3 years prior to Screening. Exceptions: adequately treated malignancies not likely to require therapy (e.g., completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma). Must be in complete remission from prior malignancy in order to be eligible to enter the study.
  • Unintended weight loss >10% in 6 months preceding study entry.
  • Electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with Bundle Branch Block (BBB) over 3 consecutive ECGs).
  • Potential participants who, in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
  • Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection; Clinically significant cardiac disease; Inadequate pulmonary function; Interstitial lung disease;
  • Active infection with HIV, HBV or HCV.
  • Pregnant or breastfeeding.